Risk Stratification and Factors in Selecting Therapy in RCC


Shared insight on the patient and disease factors that inform the selection of therapy for favorable-risk renal cell carcinoma.


Robert J. Motzer, MD:Now in this patient, you decided to go with the TKI/IO [tyrosine kinase inhibitor/immuno-oncology] therapy. What were the factors in your decision to move on with systemic therapy?

Chung-Han Lee, MD:We observe the patients for as long as possible. The ability to save people the potential of toxicity is in line with what we want to accomplish for the patients. For this patient, given the fact that she had multiple lung nodules and some of them were fairly close to her airways, having watched her for a period of time, I was starting to get concerned that we would be thinking about some intervention soon. That’s where we come into the discussion with the patients about, is the timing right, right now vs do you want to hold off? It’s certainly a much longer discussion. Given that she had favorable-risk disease, giving a TKI/IO combination would be reasonable, knowing that TKI/IOs are approved across all disease risk categories, with fairly long progression-free survival associated with that.

Robert J. Motzer, MD: One of the questions that comes up, Maria, is do you need the IO here? In the trials that were conducted, in the favorable-risk group, people cite a lack of survival in that subset and say, “I’m not so sure you need the IO.” What’s your sense on that, or your opinion in terms of would you have just treated this patient with pazopanib rather than lenvatinib and pembrolizumab?

Maria I. Carlo, MD: I would not. If there’s no contraindication to IO, there is a subset of patients with good risk who benefit from IO, and unfortunately, we can’t tell what subset that is yet. Unless there is a contraindication, based on the trials all showing, in the intention-to-treat population at least, superiority of the combination over single-agent sunitinib, I use combination TKI/IO.

Robert J. Motzer, MD: The last point on this case that we should touch base on, Joe, maybe you can comment on, we break patients down, divide them by this IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk, but as a leader in translational oncology, it seems to be reflecting underlying biology. Do you want to comment in terms of differences in underlying biology between the favorable-risk group and the intermediate/poor-risk group and how we see this come out in our therapies?

Chung-Han Lee, MD:In terms of the different risk classifications we have right now, we’ve done this essentially based off of clinical risk stratification. Our ability to risk-stratify patients by underlying biology and molecular pathways remains in its infancy. There are still a lot of challenges that we have to truly stratify this. Part of the complication from things like the risk stratification schemes is our incorporation of, for example, time from nephrectomy to time to systemic therapy. That is a risk factor that’s influenced by certain things that can be reflective of poor follow-up with health care providers. We still need to do a lot more work from a biomarker development standpoint. At least right now, most of the genomic biomarkers have not demonstrated clear utility. Based off of several analyses of the phase 3 studies, we’ve seen things RNA sequencing in gene expression profiles as something that potentially has some ability to stratify people based off their outcome. Various immune-related gene stratification schemes and angiogenesis stratification schemes do seem to correlate with the various treatments. However, that part still takes more time and more studies to think about how to best integrate that into clinical practice.

Transcript edited for clarity.

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